Project Summary Although it is widely known that people with psychosis (PSY) exhibit impairment in a number of cognitive domains?and working memory (WM) in particular?interventions aimed at remediating these deficits have been only modestly successful, and mixed results continue to emerge. One critical barrier to increasing the effectiveness of these interventions is the lack of clarity regarding neurobiological mechanisms that give rise to these impairments, and that can be used as treatment targets for intervention development. We suggest that one reason for this lack of clarity is that WM is frequently studied as a unitary phenomenon, when in fact it is dependent upon several cognitive sub-processes?each of which is supported by a unique neural process, and any one or any set of which may be impaired in PSY. In the present proposal, we will evaluate the role that a promising oscillatory candidate biomarker (alpha desynchronization) plays in constraining WM capacity in PSY. Then, using neurofeedback, we will train participants to modulate this signal and evaluate the impact of this training on visual WM retention. Recently, we and others have demonstrated that robust task-related alpha desynchronization is associated with higher memory capacity among healthy control subjects during a WM task. Furthermore, PSY exhibit robust impairments in this oscillatory process, indicating that it is a strong candidate mechanism by which WM capacity is constrained in this population. However, because a typical WM task is unable to distinguish between the various cognitive sub-processes that support WM, it is not yet known which of these sub- processes is linked to impaired alpha desynchronization in PSY. In the proposed study, we aim to identify the disrupted sub-process that is reflected in impaired alpha desynchronization in PSY (Aim 1), and further evaluate the causal relationship between this brain process and WM storage by manipulating alpha synchronization using neurofeedback (Aim 3). Additionally, we will determine the extent to which impaired alpha desynchronization is specific to psychotic illness, and the degree to which it is impacted by illness chronicity (Aim 2). Finally, in an Exploratory Aim 4, we will also measure a secondary oscillatory biomarker, theta-gamma phase amplitude coupling, which has previously been linked to the maintenance of a memory trace during the delay interval of a WM task. Our overall goal is to clarify the mechanistic role that alpha desynchronization plays in constraining WM capacity in PSY and its impact on downstream neural processes (i.e., theta-gamma phase amplitude coupling), which will lay the groundwork for future development of precision interventions that may effectively target these processes to yield improvements in WM among PSY.